Myeloperoxidase-derived oxidants rapidly oxidize and disrupt zinc-cysteine/histidine clusters in proteins

► Myeloperoxidase generates oxidants (HOCl, HOSCN, HOBr) at sites of inflammation. ► These oxidants react very rapidly with yeast alcohol dehydrogenase (YADH). ► Oxidation occurs at the active-site Zn2+-Cys/His cluster of YADH. ► This results in loss of activity and protein Cys and in dimerization and Zn2+ release. ► Zn2+-Cys/His clusters are potentially major targets for peroxidase-derived oxidants.